The study of rare cells, such as circulating tumor cells (CTCs), may aid in detection, diagnostics, and prognosis of diseases as well as in clinical care and drug discovery. For example, isolation and analysis of circulating tumor cells can be important for determining the origin of a tumor or understanding the process of tumor metastasis. Rare cells may be hard to capture due to their relatively low abundance in blood samples. Rare cells, like circulating tumor cells, may be fragile. A variety of techniques, such as immuno-magnetic isolation, cell-size based filtration, antibody-functionalized microfluidic devices, fiber-optic array scanning technology, dielectrophoresis, passive cell sorting, negative selection, ensemble-decision aliquot ranking for isolating rare cells may have a low limit of detection and/or variation in reproducibility of results. Thus, there is a need for systems and methods for isolating rare cells such as CTCs in a format that is compatible with subsequent molecular analyses and clinical utility in detection of cancers and other diseases.